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Investigation of the palatine approach as a novel technique to block the canine maxillary nerve: a comparative cadaveric study
No full text
Objectives
To develop a palatine approach to the canine maxillary nerve and compare its feasibility and the spread of dye and contrast medium with that of the infraorbital technique.
Materials and Methods
Ten canine cadaveric heads were used in this study. The maxillary nerve was approached bilaterally by inserting hypodermic needles into either the infraorbital or the palatine foramen on each side. Dye/contrast injections (1:1 solution) were followed by CT and anatomical dissections, performed to isolate the maxillary nerves and measure their stained portions. Procedural failure was defined as a nerve stain <6 mm in length. Descriptive statistics, analysis of proportions and comparison of either means or medians were used for data analysis.
Results
The stained portion of the maxillary nerve was shorter for the palatine technique (0 (0 to 10) mm) than the infraorbital technique (35 (17 to 52) mm) (
P
= .015). Procedural failure rate was higher for the palatine technique (80%) compared to the infraorbital technique (20%;
P
= .025). For both techniques, imaging showed contrast spread along the nerve pathway in 70% of injections. Contrast medium contamination of nasal turbinates and nasal passages did not differ between approaches and was observed in 50% of palatine and 30% of infraorbital injections (
P
= .057).
Clinical Significance
The novel palatine approach produced a higher procedural failure rate than the infraorbital technique and cannot be recommended as a suitable alternative to existing methods for canine maxillary nerve block.
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Examining the associations of physical activity prevalence with gross domestic product and Fragile state index: A 51-country study.
Get PDFTo describe the prevalence of physical activity and assess its correlation with a unidimensional economic measure (per capita gross domestic product - GDP) and a multidimensional measure of countries' fragility (Fragile States Index). Physical activity was measured using data from STEPwise Approach to Noncommunicable Disease Risk-Factor Surveillance calculated at individual level. We obtained the following indicators: total physical activity, any leisure-time, any transport and any work physical activity. GDP and FSI were obtained from the World Bank and the Fund for Peace respectively. An analysis was carried out to verify the relationship between physical activity and GDP/FSI. We included data from 51 countries. The prevalence of meeting physical activity recommendations was 82.6%, while for any leisure-time, any transportation and any work, the proportions were 23.6%, 73.0% and 60.5%, respectively. For any leisure-time physical activity, the lower the prevalence of the outcome the higher the fragility of countries (r = -0.55). In contrast, for any work physical activity, the pattern was inverse (r = 0.35). Our results underscore the relevance of contextual correlates of domain-specific physical activity and emphasise the need to reconsider the meaning of physical activity in each location, accounting for its different domains in promotion efforts
Interoceptive ability is uncorrelated across respiratory and cardiac axes in a large scale psychophysical study.
Get PDFInteroception, the perception of internal bodily signals, is thought to be fundamental for emotional regulation and cognitive functioning. While previous studies have indicated a degree of shared variance in interoceptive processes across cardiac and respiratory systems, evidence remains limited due to methodological constraints and small sample sizes. This study aimed to investigate individual differences in cardiac and respiratory interoception, as well as auditory exteroception across sensitivity, precision, and metacognition using consistent psychophysical approaches. In a sample of 241 participants, we found no significant correlations between cardiac and respiratory interoceptive dimensions, with the exception of a modest positive association in subjective confidence. Bayesian analyses provided moderate evidence supporting the absence of correlations across most dimensions except confidence, suggesting that interoceptive processes may be largely modality-specific, while subjective confidence may be more domain-general. These findings refine theoretical models of interoception and highlight the importance of modality-specific psychophysical approaches in both cognitive and clinical research on interoceptive ability
Bayesian model averaging for partial ordering continual reassessment methods
No full textSummary: Phase I clinical trials are essential to bringing novel therapies from chemical development to widespread use. Traditional approaches to dose-finding in Phase I trials, such as the ‘3 + 3’ method and the continual reassessment method (CRM), provide a principled approach for escalating across dose levels. However, these methods lack the ability to incorporate uncertainty regarding the dose-toxicity ordering as found in combination drug trials. Under this setting, dose levels vary across multiple drugs simultaneously, leading to multiple possible dose-toxicity orderings. The CRM for partial ordering (POCRM) extends to these settings by allowing for multiple dose-toxicity orderings. In this work, it is shown that the POCRM is vulnerable to ‘estimation incoherency’ whereby toxicity estimates shift in an illogical way, threatening patient safety and undermining clinician trust in dose-finding models. To this end, the Bayesian model averaged POCRM (BMA-POCRM) is formalized. BMA-POCRM uses Bayesian model averaging to take into account all possible orderings simultaneously, reducing the frequency of estimation incoherencies. We derive novel theoretical guarantees on the estimation coherency of the POCRM and BMA-POCRM. The effectiveness of BMA-POCRM in drug combination settings is demonstrated through a specific instance of estimate incoherency of POCRM and simulation studies. The results highlight the improved safety, accuracy, and reduced occurrence of estimate incoherency in trials applying the BMA-POCRM relative to the POCRM model
Utilizing Constrained Bicyclic Peptides for In Vitro Diagnostics.
No full textConstrained bicyclic peptides (Bicycle molecules) with high affinity for biological targets have emerged as potentially powerful therapeutic agents, particularly for the in vivo targeting of cancer receptors. However, their antibody-mimetic properties have yet to be explored for use in diagnostic immunoassays. These synthetically derived compounds serve as biorecognition scaffolds that allow for facile site-selective modification and large-scale production. A phage display screen against various constructs of the SARS-CoV-2 nucleocapsid (N) protein identified several Bicycle molecules with binding affinities ranging from the micromolar to the low nanomolar range. These Bicycle molecules were validated in the development of enzyme- and nanozyme-linked immunosorbent assays, as well as enzymatic and colorimetric nanoparticle-based lateral flow immunoassays (LFIA) for the detection of ultralow concentrations of the SARS-CoV-2 N protein. We envision that these moieties enable robust, cost-effective, and large-scale development of ultrasensitive biosensors for a diverse range of biomarkers by leveraging their high binding affinity, minimalistic scaffold, and synthetic accessibility
Rotational mobility in spherical membranes: the interplay between Saffman–Delbrück length and inclusion size
No full textThe mobility of particles in fluid membranes is a fundamental aspect of many biological and physical processes. In a 1975 paper (Saffman PG, Delbrück M. 1975 Brownian Motion in Biological Membranes. Proc. Natl Acad. Sci. USA72, 3111–3113. (doi:10.1073/pnas.72.8.3111)), Saffman and Delbrück demonstrated how the presence of external Stokesian solvents is crucial in regularizing the apparently singular flow within an infinite flat membrane. In the present paper, we extend this classical work and compute the rotational mobility of a rigid finite-sized particle located inside a spherical membrane embedded in Stokesian solvents. Treating the particle as a spherical cap, we solve for the flow semi-analytically as a function of the Saffman–Delbrück (SD) length (ratio of membrane to solvent viscosity) and the solid angle formed by the particle. We study the dependence of the mobility and flow on inclusion size and SD length, recovering the flat-space mobility as a special case. Our results will be applicable to a range of biological problems including rotational Brownian motion, the dynamics of lipid rafts, and the motion of aquaporin channels in response to water flow. Our method will provide a novel way of measuring a membrane’s viscosity from the rotational diffusion of large inclusions, for which the commonly used planar Saffman–Delbrück theory does not apply
Static Black Binaries in de Sitter Space.
No full textWe construct the first four-dimensional multiple black hole solution of general relativity with a positive cosmological constant. The solution consists of two static black holes whose gravitational attraction is balanced by the cosmic expansion. These static binaries provide the first four-dimensional example of nonuniqueness in general relativity without matter
Extremal Kerr Black Holes as Amplifiers of New Physics.
No full textWe show that extremal Kerr black holes are sensitive probes of new physics. Stringy or quantum corrections to general relativity are expected to generate higher-curvature terms in the gravitational action. We show that in the presence of these terms, asymptotically flat extremal rotating black holes have curvature singularities on their horizon. Furthermore, near-extremal black holes can have large yet finite tidal forces for infalling observers. In addition, we consider five-dimensional extremal charged black holes and show that higher-curvature terms can have a large effect on the horizon geometry
Digital cognition plus plasma p-Tau217 and Aβ42/40 powerfully predict Alzheimer's progression.
No full textINTRODUCTION: Alzheimer's disease is characterized by amyloid-β (Aβ) and tau accumulation. Identifying individuals with rapid proteinopathy progression is crucial for timely intervention and trial enrichment. METHODS: We analyzed longitudinal data from 456 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, including 375 with digital cognitive test scores. Amyloid and tau accumulation rates were estimated from positron emission tomography (PET) imaging using linear mixed-effects models. Participants were classified as fast or slow accumulators via Gaussian modeling. Predictors of accumulation and clinical conversion were assessed with logistic and Cox regression models, incorporating demographics, cognitive measures and plasma biomarkers. RESULTS: Plasma p-tau217 and Aβ42/Aβ40 predicted rapid accumulation and conversion, with p-tau217 the strongest marker (odds ratio [OR] up to 6.6). Baseline digital cognitive measures contributed significantly to the prediction, achieving comparable or superior predictive accuracy to traditional cognitive tests (area under the curve [AUC] up to 0.92; C-index 0.82). DISCUSSION: Plasma p-tau217 and Aβ42/Aβ40 emerged as robust predictors of the progression of disease pathology, supported by cognitive measures
Integrating public engagement to promote transparent data use in a new UK-wide birth cohort.
No full textPublic engagement is an important mechanism for ensuring that the voices of the public are integrated into study design and data use. The commissioning of a new UK-wide birth cohort study by the UKRI Economic and Social Research Council (ESRC), the Early Life Cohort Feasibility Study (ELC-FS), necessitated renewed dialogue with the public about the acceptability of conducting a large-scale study of this kind. The ELC-FS recruited several thousand children in their first year of life, using an administrative data sampling frame, an 'opt-out' recruitment approach, and embedded linkages to education, health and social care administrative data. The study faced many complexities and challenges to achieve this: the sampling frame had not been used for this purpose before, required negotiation with different data holders in the four UK nations, and the study needed to ensure transparency around how participants' administrative and survey data would be used. Conducting public engagement projects with parents of young children prior to the study's fieldwork was essential to understanding more about the public acceptability of data use in ELC-FS. Evidence from these projects was used to support negotiations with data holders, as well as in guiding best practice for informing participants about their data use and data linkage. This paper summarises the evidence from these public engagement projects relating to data transparency and enacting participant choice and control of the use of their data in the study. We describe how this evidence was implemented in three key study design areas: sampling and recruitment, the collection and use of survey data, and seeking participant consent to link administrative records to individual-level survey data. We also present evidence from the study's fieldwork about participants' acceptability of the survey design and transparency around data use, from recruitment to data collection and processing